PMID- 26423989 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151229 LR - 20220408 IS - 2352-3018 (Electronic) IS - 2352-3018 (Linking) VI - 1 IP - 2 DP - 2014 Nov TI - Effect of the CCR5 antagonist maraviroc on the occurrence of immune reconstitution inflammatory syndrome in HIV (CADIRIS): a double-blind, randomised, placebo-controlled trial. PG - e60-7 LID - S2352-3018(14)70027-X [pii] LID - 10.1016/S2352-3018(14)70027-X [doi] AB - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in patients with HIV. IRIS is associated with an increased risk of admission to hospital and death. We assessed whether CCR5 blockade with maraviroc reduces the risk of IRIS. METHODS: The CADIRIS study was a double-blind, randomised, placebo-controlled trial that recruited participants from five clinical sites in Mexico and one in South Africa and followed them for 1 year. Patients were eligible if they were adults with HIV, who were naive to ART, had CD4 count lower than 100 cells per muL and HIV RNA greater than 1000 copies per mL. Participants were randomly assigned (1:1) by permuted block randomisation to receive either maraviroc (600 mg twice daily) or placebo in addition to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Patients, care providers, and members of the research team were masked to treatment allocation. Clinical and laboratory evaluations were done at baseline, and weeks 2, 4, 8, 12, 16, 24, 48, and 60. The primary outcome was time to an IRIS event by 24 weeks. All patients who were randomly assigned contributed to the primary time-to-event analysis from the date of ART initiation until week 24, the time of an IRIS event or death. This trial is registered with ClinicalTrials.gov, number NCT00988780. FINDINGS: Between Dec 10, 2009, and Jan 17, 2012, we screened 362 patients; of whom 279 met the inclusion criteria and three refused to participate; thus 276 participants were randomly assigned (140 to receive maraviroc and 136 to receive placebo). 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc group and 31 (23%) in the placebo group (p=0.74). No difference in the time to IRIS events was noted between the treatment groups (HR 1.08, 95% CI 0.66-1.77; log-rank test p=0.74). 37 participants (26%) in the maraviroc group had grade 3 or 4 adverse events compared with 24 (18%) in placebo group; p=0.072); 25 (18%) in the maraviroc group and 21 (15%) in the placebo group had serious treatment emergent adverse events (p=0.63). INTERPRETATION: Maraviroc had no significant effect on development of IRIS after ART initiation. Inclusion of this CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in people with advanced HIV infection. FUNDING: Pfizer. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Sierra-Madero, Juan G AU - Sierra-Madero JG AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran", Mexico DF, Mexico. FAU - Ellenberg, Susan S AU - Ellenberg SS AD - Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Rassool, Mohammed S AU - Rassool MS AD - Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. FAU - Tierney, Ann AU - Tierney A AD - Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Belaunzaran-Zamudio, Pablo F AU - Belaunzaran-Zamudio PF AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran", Mexico DF, Mexico. Electronic address: p_belaunzaran@yahoo.co.uk. FAU - Lopez-Martinez, Alondra AU - Lopez-Martinez A AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran", Mexico DF, Mexico. FAU - Pineirua-Menendez, Alicia AU - Pineirua-Menendez A AD - Departmento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran", Mexico DF, Mexico. FAU - Montaner, Luis J AU - Montaner LJ AD - HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA. FAU - Azzoni, Livio AU - Azzoni L AD - HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA. FAU - Benitez, Cesar Rivera AU - Benitez CR AD - Servicio de Infectologia, Hospital General de Mexico, Mexico DF, Mexico. FAU - Sereti, Irini AU - Sereti I AD - HIV Pathogenesis Unit, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD, USA. FAU - Andrade-Villanueva, Jaime AU - Andrade-Villanueva J AD - Unidad de VIH, Hospital Civil de Guadalajara, Guadalajara, Jalisco, Mexico. FAU - Mosqueda-Gomez, Juan L AU - Mosqueda-Gomez JL AD - Centro Ambulatorio para la Prevencion y Atencion del SIDA e Infecciones de Transmision Sexual, Leon, Guanajuato, Mexico. FAU - Rodriguez, Benigno AU - Rodriguez B AD - Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA. FAU - Sanne, Ian AU - Sanne I AD - Clinical HIV Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. FAU - Lederman, Michael M AU - Lederman MM AD - Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA. CN - CADIRIS study team LA - eng SI - ClinicalTrials.gov/NCT00988780 PT - Journal Article DEP - 20141021 PL - Netherlands TA - Lancet HIV JT - The lancet. HIV JID - 101645355 EIN - Lancet HIV. 2015 Oct;2(10):e416 EDAT- 2015/10/02 06:00 MHDA- 2015/10/02 06:01 CRDT- 2015/10/02 06:00 PHST- 2015/10/02 06:00 [entrez] PHST- 2015/10/02 06:00 [pubmed] PHST- 2015/10/02 06:01 [medline] AID - S2352-3018(14)70027-X [pii] AID - 10.1016/S2352-3018(14)70027-X [doi] PST - ppublish SO - Lancet HIV. 2014 Nov;1(2):e60-7. doi: 10.1016/S2352-3018(14)70027-X. Epub 2014 Oct 21.